Chlamydial Pathogeneis in the Reproductive Tract

生殖道中的衣原体致病菌

• 批准号: 7762440
• 负责人: PATRIK M BAVOIL
• 金额: $ 33.68万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-21 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762440
• 关键词: Address; Antibody Formation; Cavia; Cell Death; Cell Line; Cells; Cervical; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Collaborations; Complex; Cytosol; Development; Ecology; Environment; Epithelial Cells; Female; Frequencies; Gene Family; Genes; Genital system; Genomics; Germ-Free; Health; Human; Immune; In Vitro; Infection; Infertility; Inflammatory Response; Intervention; Investigation; Knowledge; Laboratories; Laboratory Study; Measurable; Measures; Membrane; Membrane Proteins; Methods; Microbe; Modeling; Molecular Target; Mus; Pathogenesis; Pathology; Patients; Pelvic Inflammatory Disease; Phase; Physiological; Play; Process; Property; Proteins; Reproductive Tract Infections; Research; Risk; Role; Serum; Swab; System; Therapeutic; Translational Research; Type III Secretion System Pathway; Vaccines; Vagina; Variant; Virulence; Virulence Factors; Woman; cohort; design; genome sequencing; member; pathogen; reproductive; response; trafficking; trait; vaccine development; ward

The objective of this project (2) is to characterize essential correlates of chlamydial infection of the human reproducfive tract jn the human reproductive tract. This will prime effective translational research through the identificafion and characterizafion of chlamydial anfigens of relevance to vaccine development and of physiologic or pathogenefic mechanisms that are at play in the complex, natural environment of the female genital tract and provide targets for possible chemotherapeutic intervenfion. The project involves extensive collaboration with the complementary projects 1 and 3 of the CRC and will rely on Cores B, C and D for the provision of guinea pig and human sera and swabs, and biostafistical analysis of the results, respectively. In a first phase, the virulence of C. trachomatis and C. cawae genital isolates will be quantified in relafionship to genome sequence type and reproductive tract ecology using a pafient cohort representative of genital chlamydial disease in humans. Virulence will be measured using genomic doubling, infecfious yield, inclusion fusogenicity and pathology as measurable physiological/pathogenic traits or endpoints, and using biomathemafical modeling of Intracellular development and correlated pathology. A second phase of the research will be to investigate in relationship to genome sequence type and reproducfive tract ecology the funcfional diversity of two gene families of C. trachomatis and C. caviae encoding inclusion membrane proteins (Inc) and effector proteins of the virulence-associated type III secretion (T3S) system that are targets for possible chemotherapeutic intervention. The developmental expression of selected inc and T3S effector genes in variants of C. trachomatis and C. cawae will be characterized and subcellular and molecular targets of variant Inc and T3S effector proteins will be identified. Finally, the diversity of the vaccine target pmp gene family and Pmp-specific antibody responses in C. /rac/7omaf/s-infected patients and C. cawae-infected guinea pigs will be investigated in relationship to genome sequence type and reproducfive tract ecology. This will be achieved through characterization of the developmental expression of pmp genes in variants of C. trachomatis and C. cawae, profiling the high frequency on/off switching of Pmp expression in selected variants and performing cross-sectional and longitudinal invesfigafions of the Pmp-specific anfibody response comparatively in infected humans and guinea pigs.

本项目的目的（2）是描述人类衣原体感染的基本相关因素， 人类生殖道中的生殖道。这将推动有效的翻译研究， 与疫苗开发相关的衣原体抗原的鉴定和表征， 在女性复杂的自然环境中起作用的生理或致病机制 为可能的化疗干预提供靶点。该项目涉及广泛 与化学品审查委员会的补充项目1和3合作，并将依靠核心项目B、C和D， 分别提供豚鼠和人血清和拭子，并对结果进行生物统计学分析。 在第一阶段，C.沙眼衣原体和沙眼衣原体。cawae生殖器分离株将在相关的 基因组序列类型和生殖道生态学使用一个pafient队列代表生殖器 人类的衣原体疾病毒力将使用基因组加倍、感染产量、 包括融合性和病理学作为可测量的生理/致病性状或终点，并使用 细胞内发育和相关病理学的生物热模拟。 研究的第二阶段将是调查基因组序列类型和 生殖道生态学研究表明，两个基因家族的功能多样性与生殖道生态学有关。沙眼衣原体和沙眼衣原体。caviae 编码包含膜蛋白（Inc）和毒力相关III型效应蛋白 分泌（T3 S）系统，其是可能的化疗干预的靶标。发育 选择的inc和T3 S效应基因在C.沙眼衣原体和沙眼衣原体。卡瓦埃将是 将鉴定变体Inc和T3 S效应蛋白的亚细胞和分子靶标。 最后，研究了疫苗靶基因pmp家族的多样性和肺炎克雷伯菌中Pmp特异性抗体应答。 /rac/7 omaf/s感染者和C.将对感染卡瓦病毒的豚鼠进行与以下疾病的关系进行研究 基因组序列类型和生殖道生态。这将通过表征 pmp基因在C.沙眼衣原体和沙眼衣原体。cawae，剖析高 在所选变体中Pmp表达的频率开/关转换，并进行横截面和 在感染人群中比较Pmp特异性抗体应答的纵向研究， 豚鼠